NGC-Cap Demonstrates Preliminary Efficacy in Stage III/IV GI Cancer

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Next-generation capecitabine (NGC-Cap), comprised of the combination of capecitabine and PCS6422, generated preliminary efficacy in patients with stage III or IV gastrointestinal (GI) cancer, according to preliminary data from the phase 1b NGC-Cap trial (NCT04861987).

Findings announced in a news release from Processa Pharmaceuticals showed that in patients who were treated with 1 dose of PCS6422 and 7 days of capecitabine (n = 12), 66.7% experienced a partial response (PR; n = 2) or stable disease (SD; n = 6). In these patients, progression-free survival (PFS) ranged from approximately 5 to 11 months.

Furthermore, patients (n = 3) treated with the maximum tolerated dose (MTD) of capecitabine at 225 mg twice per day following a single dose of PCS6422 achieved PFS ranging from approximately 5 to 7 months. At 150 mg of capecitabine twice per day following a single dose of PCS6422 (n = 3), 2 patients had SD, and PFS for these patients ranged from 3 to 7 months.

“We are encouraged by the preliminary efficacy analysis from our NGC-Cap phase 1b dose-escalating safety/tolerability trial demonstrating some antitumor activity in patients with advanced GI cancer who have progressive cancer after relapsing or not responding to prior therapy,” David Young, PharmD, PhD, president of Research and Development at Processa Pharmaceuticals, stated in a news release. “The favorable response is likely due to NGC-Cap’s ability to distribute more 5-fluorouracil [5-FU] to cancer cells than monotherapy capecitabine. The promising phase 1b safety and tolerability profile plus these early efficacy signals provide validation for further development of NGC-Cap.”

NGC-Cap combines PCS6422, an irreversible dihydropyrimidine dehydrogenase (DPD) inhibitor, with low doses of capecitabine. Capecitabine, the oral form of 5-FU, is one of the most widely used chemotherapy drugs for the treatment of patients with solid tumors. Following oral ingestion, capecitabine is metabolized into 5-FU, which breaks down into anabolites and catabolites. Although anabolites actively kill duplicating cells, catabolites only cause adverse effects (AEs). DPD plays a role in the unwanted conversion of 5-FU into catabolites.

As a single agent, PCS6422 is neither toxic nor active in animals at comparable doses. However, when combined with capecitabine or 5-FU, PCS6422 reduces the metabolism of 5-FU into catabolites, thereby allowing more 5-FU to reach and attack the cancer cells.

The phase 1b trial evaluated increasing doses of capecitabine administered following a single dose of PCS6422 in patients with stage III or IV, advanced, relapsed or refractory, progressive GI cancer. To be eligible for the trial, all patients needed to have relapsed or progressive disease following other treatments, including previous capecitabine or 5-FU.

Additional data from the study showed that all dose levels of capecitabine in NGC-Cap were associated with greater exposure of 5-FU and lower exposure of fluoro-beta-alanine, with a better or similar AE profile compared with capecitabine monotherapy.

“Given the need for more effective chemotherapy treatment with improved tolerability across multiple types of cancer, we believe that NGC-Cap has the potential to provide a safer, more efficacious option to treat the different cancers for which capecitabine and 5-FU are presently used,” Young said in the press release.

These dosing regimens will continue to be evaluated in a phase 2 trial for patients with breast cancer in order to determine the optimal dose of NCP-Cap.

“From this phase 1b trial, we have been able to define the MTD and the recommended phase 2 dose to use in our phase 2 optimal dosage regimen trial in breast cancer in the third quarter of 2024,” Young added.

Reference

Processa Pharmaceuticals announces positive efficacy results from preliminary evaluation of phase 1b dose-escalating trial with NGC-Cap in gastrointestinal cancer. News release. Processa Pharmaceuticals. June 12, 2024. Accessed June 12, 2024. https://www.processapharmaceuticals.com/news-media/press-releases/detail/122/processa-pharmaceuticals-announces-positive-efficacy